Alkaline phosphatase downregulation promotes lung adenocarcinoma metastasis via the c-Myc/RhoA axis.

BACKGROUND: Lung adenocarcinoma (LUAD) metastasis significantly reduces patient survival; hence inhibiting the metastatic ability of lung cancer cells will greatly prolong patient survival. Alkaline phosphatase (ALPL), a homodimeric cell surface phosphohydrolase, is reported to play a controversial role in prostate cancer and ovarian cancer cell migration; however, the function of ALPL in LUAD and the related mechanisms remain unclear. METHODS: TCGA database was used to analysis the expression of ALPL, and further verification was performed in a cohort of 36 LUAD samples by qPCR and western blot. Soft-agar assay, transwell assay and lung metastasis assay were employed to detect the function of ALPL in LUAD progression. The qPCR, luciferase promoter reporter assay and western blot were used to clarify the molecular mechanisms of ALPL in promoting metastasis in LUAD. RESULTS: ALPL was downregulated in LUAD, and the disease-free survival rate of patients with low ALPL was significantly reduced. Further studies showed that overexpression of ALPL in LUAD cell lines did not significantly affect cell proliferation, but it did significantly attenuate lung metastasis in a mouse model. ALPL downregulation in LUAD led to a decrease in the amount of phosphorylated (p)-ERK. Because p-ERK promotes the classical c-Myc degradation pathway, the decrease in p-ERK led to the accumulation of c-Myc and therefore to an increase in RhoA transcription, which enhanced LUAD cell metastasis. CONCLUSION: ALPL specially inhibits the metastasis of LUAD cells by affecting the p-ERK/c-Myc/RhoA axis, providing a theoretical basis for the targeted therapy of clinical LUAD.

Efficacy of Bronchoalveolar Lavage as Adjunct Therapy in the Treatment of Neonatal Severe Pneumonia: A Prospective Case-Control Study.

OBJECTIVE: The aim of this study was to investigate the efficacy and safety of bronchoalveolar lavage (BAL) in the treatment of neonatal severe pneumonia (NSP). METHODS: One hundred patients with severe pneumonia were randomly divided into two groups, the BAL and control groups, with 50 patients in each group. In the BAL group, normal saline was instilled into the endotracheal tube for BAL. Before and after lavage, lung ultrasound (LUS) monitoring was performed to observe the lung pathological changes. Conventional treatment was administered in the control group. The need for and duration of invasive mechanical ventilation, the complication rate, the duration and cost of hospitalization and the mortality rate were compared between the two groups. RESULTS: The results of this study showed that there were 35 (70%) patients who meet the indications of the invasive mechanical ventilation (IMV) at admission in the BAL group, while there were only 15 (30%) patients still requiring IMV after BAL therapy. The duration of IMV was 41.7 ± 7.5 vs. 97.7 ± 12.9 h in BAL and controls, the incidence rate of complications was 8.0% vs. 20.0% in both groups, the length of hospital stay was 9.2 ± 1.9 vs. 14.1 ± 2.1 days in both groups, and the expense of hospital cost was 12 557 ± 832 vs. 19 121 ± 929 Chinese Yuan in both groups. All patients had stable vital signs during lavage, and no significant adverse side effects were observed. CONCLUSION: BAL was significantly beneficial for NSP with no significant adverse side effects; LUS is a useful tool for the timely detection of BAL effects.

The relationship between LRP5 rs556442 and rs638051 polymorphisms and mutations and their influence on bone metabolism in postmenopausal Xinjiang women with type 2 diabetes.

BACKGROUND: The Wnt/ß-catenin signaling pathway plays a crucial role in bone development and metabolism. The low-density lipoprotein receptor-related protein 5 (LRP5), an important receptor in the Wnt signaling pathway, promotes the osteogenesis of osteoblasts and curbs bone resorption by osteoclasts. OBJECTIVES: To determine the expression of LRP5 polymorphisms (rs556442 and rs638051) and their relationship with bone mineral density (BMD) and bone metabolism markers in postmenopausal patients with type 2 diabetes mellitus (T2DM) in Xinjiang, China. MATERIAL AND METHODS: According to dual-energy X-ray (DEXA) and oral glucose tolerance test (OGTT) results, 226 postmenopausal women from Xinjiang were divided into the following groups: normal glucose tolerance (NGT) + normal bone mass group (group A), NGT + abnormal bone mass group (group B), T2DM + normal bone mass group (group C), and T2DM + abnormal bone mass group (group D). RESULTS: Femoral neck BMD was lower in group B women with the AG/GG genotype (mutant type) compared to women with the AA genotype (wild-type) at rs556442. Alkaline phosphatase (ALP) levels were lower in group D women with the AG/GG genotype (mutant type) compared to women with the AA genotype (wild-type) at rs556442 and rs638051. The factors influencing BMD (lumbar spine vertebrae 1-4 (L1-L4)) were triglyceride (TG) levels, body mass index (BMI), menopausal transition age, and age for rs556442 patients, and TG levels and menopausal transition age for rs638051 patients in group D. The factors affecting BMD (hip) were TG levels, BMI and age for rs556442 patients, and TG levels and age for rs638051 patients. CONCLUSIONS: The LRP5 gene mutations are linked to bone metabolism disorders in postmenopausal women with T2DM and abnormal bone mass. High BMI and TG were positively associated with BMD, while increased age and menopausal transition age were negatively associated with BMD.

Study on the quality and inkjet printing effect of the prepared washing-free disperse dye ink.

With the rapid development of digital inkjet printing, it will inevitably lead to the uneven quality of inkjet printing ink products on the market. Therefore, making a more comprehensive and accurate quality evaluation of digital printing ink is particularly important. In this study, a short process and environment-friendly washing-free disperse dye ink was prepared based on the research on ink quality. The quality of printing ink is closely related to its physical properties, printing ink stability, inkjet performance, and inkjet printing effect. The microdistribution state of water for washing-free disperse dye ink was analyzed by LF-NMR, and the influence of the microstate of water on the macro physical properties of the ink was clarified. The physical properties (particle size, pH value, surface tension, viscosity, rheological properties, etc.) of the washing-free disperse dye ink were systematically tested and analyzed. At the same time, the stability (weatherability, the temperature sensitivity of viscosity, and shear stability) and inkjet performance (drive waveform A, B, and C) of washing-free disperse dye ink were systematically investigated. Finally, the inkjet printing effect of washing-free disperse dye ink was evaluated. This study systematically examined the quality and printing effect of the prepared washing-free disperse dye ink and provided quality evaluation reference for the development of high-quality washing-free disperse dye ink.

Analysis of Distributions of HPV Infection in Females with Cervical Lesions in the Western District of Beijing Chaoyang Hospital.

Objective: To analyze the distribution of human papilloma virus (HPV) infection in women with cervical lesions of different grades and analyze the relationship of high-risk HPV and cervical lesions in order to facilitate targeted prevention. Methods: The infection status of HPV subtype was statistically analyzed in patients who underwent colposcopy examination from April 2017 to June 2019. Results: The infection rate of HPV was 81.4% in chronic cervicitis, 82.9% in 1ow-grade squamous intraepithelial lesion (LSIL), 63.7% in HSIL (high-grade squamous intraepithelial lesion), and 50% in cervical squamous cell carcinoma (CSCC). Among the 16 high-risk HPV types, the top six HPV types with the comprehensive infection rates were HPV16 > HPV52 > HPV58 > HPV18 > HPV51 > HPV53 in turn, and the infection rates were 23.3%, 14.8%, 13.3%, 9.8%, 9.2%, and 8.8%, respectively. The infection rates of HPV16 in chronic cervicitis group, LSIL group, and HSIL group were significantly different. There was no significant difference in the injection rates of HPV52, HPV58, and HPV18 among the three groups. HPV infection rates were highest in the 31-40 years old group, followed by the 41-50 years old group. Conclusion: The distribution of different types of HPV varies in different tissue types, which can be used to develop relevant vaccines to achieve better prevention and treatment of cervical cancer.

A Study of the Relationship between the Polymorphism and Mutation of rs682429 and rs3781590 in the LRP5 Gene and Bone Metabolism in Postmenopausal Type 2 Diabetic Women in Xinjiang.

OBJECTIVE: To explore the expression of the polymorphism and mutation of rs682429 and rs3781590 in the low-density lipoprotein receptor-related protein 5 (LRP5) genotype and to analyse the relationship of bone mineral density (BMD) and bone metabolism markers in postmenopausal women with type-2 diabetes mellitus (T2DM) in Xinjiang, China, to provide a basis for prevention and treatment of the disease. METHODS: A total of 136 postmenopausal women were included in the study. According to the results of an oral glucose tolerance test (OGTT) and dual-energy X-ray (DEXA) determination of BMD, the study subjects were divided into 4 groups: group A: normal OGTT+normal bone mass group; group B: normal OGTT+osteoporotic (OP) group; group C: T2DM+normal bone mass group; group D: T2DM+osteoporotic (OP) group. Calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and clinical biochemical data were determined; haemoglobin A1c (HbA1c) was measured by HPLC; BMD of the femoral neck, hip, and lumbar spine (L1-4) was measured by dual-energy X-ray (DEXA); and the rs682429 and rs3781590 polymorphisms of the LRP5 gene were detected by time-of-flight mass spectrometry (TOF MS). RESULTS: (1) The rs682429 polymorphism of the LRP5 genotype distribution was statistically significant (P < 0.05) in group B compared with group A. (2) The triglycerides (TG) of women with the CT/TT genotype (mutant type) were higher than those of women with the CC genotype (wild type) (2.37 ± 1.30 vs. 1.52 ± 0.83, P < 0.05) at the rs3781590 site of the LRP5 gene in group D. (3) Multiple linear regression analysis showed that TG (ß = 0.034, P < 0.05) and body mass index (BMI) (ß = 0.013, P < 0.05) were the influencing factors of BMD (L1-4) in T2DM patients. TG (ß = 0.022, P < 0.05), BMI (ß = 0.009, P < 0.05), and duration of menopause (ß = 0.005, P < 0.05) were the influencing factors of BMD (hip). CONCLUSION: (1) The rs682429 polymorphism site in the LRP5 gene may be involved in bone metabolism in postmenopausal women from Xinjiang. (2) The rs3781590 mutation in the LRP5 gene from these subjects may be involved in lipid metabolism. (3) Among postmenopausal women with type 2 diabetes mellitus and bone mass abnormality in the Xinjiang Shihezi area, high BMI and TG are protective factors against increased BMD. Duration of menopause is a risk factor for increased BMD.

Preference adjustable multi-objective NMPC: An unreachable prioritized point tracking method.

This paper proposes a new preference adjustable multi-objective model predictive control (PA-MOMPC) law for constrained nonlinear systems. With this control law, a reasonable prioritized optimal solution can be directly derived without constructing the Pareto front by solving a minimal optimization problem, which is a novel development of recently proposed utopia tracking approaches by additionally considering objective preferences with more flexible terminal and stability constraints. The tracking point of the proposed PA-MOMPC law is represented by a parametric vector with the parameters adjustable on the basis of objective preferences. The main result of this paper is that the solution obtained through the proposed PA-MOMPC law is demonstrated to have two important properties. One is the inherent Pareto optimality, and the other is the priority consistency between the solution and the tuning parametric vector. This combination makes the objective priorities tuning process transparent and efficient. The proposed PA-MOMPC law is supported by feasibility analyses, proof of nominal stability, and a numerical case study.

RhoGDIß promotes Sp1/MMP-2 expression and bladder cancer invasion through perturbing miR-200c-targeted JNK2 protein translation.

Our most recent studies demonstrate that RhoGDIß is able to promote human bladder cancer (BC) invasion and metastasis in an X-link inhibitor of apoptosis protein-dependent fashion accompanied by increased levels of matrix metalloproteinase (MMP)-2 protein expression. We also found that RhoGDIß and MMP-2 protein expressions are consistently upregulated in both invasive BC tissues and cell lines. In the present study, we show that knockdown of RhoGDIß inhibited MMP-2 protein expression accompanied by a reduction of invasion in human BC cells, whereas ectopic expression of RhoGDIß upregulated MMP-2 protein expression and promoted invasion as well. The mechanistic studies indicated that MMP-2 was upregulated by RhoGDIß at the transcriptional level by increased specific binding of the transcription factor Sp1 to the mmp-2 promoter region. Further investigation revealed that RhoGDIß overexpression led to downregulation of miR-200c, whereas miR-200c was able directly to target 3'-UTR of jnk2mRNA and attenuated JNK2 protein translation, which resulted in attenuation of Sp1mRNA and protein expression in turn, inhibiting Sp1-dependent mmp-2 transcription. Collectively, our studies demonstrate that RhoGDIß overexpression inhibits miR-200c abundance, which consequently results in increases of JNK2 protein translation, Sp1 expression, mmp-2 transcription, and BC invasion. These findings, together with our previous results showing X-link inhibitor of apoptosis protein mediating mRNA stabilization of both RhoGDIß and mmp-2, reveal the nature of the MMP-2 regulatory network, which leads to MMP-2 overexpression and BC invasion.

[A study on the diagnosis and etiology of cerebral venous thrombosis].

OBJECTIVE: To determine the clinical characteristic and common etiologies of cerebral venous thrombosis (CVT) in China. METHODS: Clinical and neuroimaging data of 91 cases of CVT were analyzed retrospectively. RESULTS: 91 CVT patients (49 men, 42 women), aged from 9 to 57 years, were diagnosed with MRI (78 cases, 85.71%), MRA (37 cases, 40.66%) or DSA (32 cases, 35.16%). 27 cases (29.67%) had a clinical pattern of isolated intracranial hypertension, 56 cases (61.54%) of focal deficits and/or seizures, 3 cases of subacute encephalopathy and 5 cases of cavernous sinus thrombosis. Oral contraceptive was the most common cause, being found in 12 cases (13.19%). CONCLUSIONS: Understanding of the clinical characteristics of CVT and using of MRI and MRA examination as early as possible is the key in CVT diagnosis. Oral contraceptive is the most common etiology.